Stem Cell Transplantation and T-Cell Add-Back to Treat Bone Marrow Malignancies

NCT00079391 | Completed Phase 2 Results DMC

• 2 other identifiers: 04011204-H-0112
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and effectiveness of stem cell transplantation in which the donor's T cells (a type of lymphocyte, or white blood cell) are removed and then added back. Certain patients with bone marrow malignancies undergo transplantation of donated stem cells to generate new and normally functioning bone marrow. However, T-cells from the donor may see the patient's cells as foreign and mount an immune response to reject them, causing what is called "graft-versus-host-disease" (GVHD). Therefore, in this protocol, T-cells are removed from the donor cells to prevent this complication. However, because T-cells are important in fighting viral infections as well as any remaining malignant cells (called graft-versus-leukemia effect), the donor T-cells are given to the patient (added back) at a later time after the transplant when they can provide needed immunity with less risk of causing GVHD. Patients between 10 and 55 years of age with acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome may be eligible for this study. Prospective participants and their donors are screened with a medical history and physical examination, blood tests (including a test to match for genetic compatibility), breathing tests, chest and sinus x-rays, and tests of heart function. They also undergo a bone marrow biopsy and aspiration. For this procedure, done under local anesthetic, about a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone. They undergo apheresis to collect lymphocytes for research studies. This procedure involves collecting blood through a needle in the arm, similar to donating a unit of blood. The lymphocytes are then separated and removed by a cell separator machine, and the rest of the blood is returned through a needle in the other arm. Before treatment begins, patients have a central intravenous line (flexible plastic tube) placed in a vein in the chest. This line remains in place during the stem cell transplant and recovery period for drawing and transfusing blood, giving medications, and infusing the donated cells. Preparation for the transfusion includes high-dose radiation and chemotherapy. Patients undergo total body irradiation in 8 doses given in two 30-minute sessions a day for 4 days. Eight days before the transplant, they begin taking fludarabine, and 3 days before the procedure they start cyclophosphamide.

Conditions

Hematologic Malignancies; Bone Marrow Transplant Rejection

Keywords

Chronic Myelogenous Leukemia (CML); Acute Lymphoblastic Leukemia (ALL); Acute Myelogenous Leukemia (AML); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndromes (MDS); Peripheral Blood Stem Cells; Graft-Versus Leukemia/Myeloma; Graft-Versus-Host Disease (GVHD); Cyclosporine; Fludarabine; Leukemia; Myelodysplastic Syndrome; Myeloproliferative Syndrome; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• The Proportion of Patients Who Develop Full Donor T Cell Chimerism at Day 30

  The proportion of patients who develop full donor CD3+ lymphocyte chimerism by day 30. Full chimerism is defined as \>95% donor alleles by molecular profiling (Short Tandem Repeat analysis).

  Day 30

Secondary Outcomes (5)

• Overall Survival

  at 5 years post transplant

• Non Relapse Mortality.

  at 5 years post transplant

• Cumulative Incidence of Relapse

  at 5 years post transplant

• Acute Graft Versus Host Disease (Before Day 60 T Cell Add Back)

  First 60 days

• Acute GVHD Overall

  First 100 days

Study Arms (1)

allogeneic hematopoietic SCT

EXPERIMENTAL

allogeneic hematopoietic stem cell transplantation (SCT) using Nexell Isolex system

Device: allogeneic hematopoietic stem cell transplantation

Interventions

allogeneic hematopoietic stem cell transplantation DEVICE

Manipulated Peripheral Blood Stem Cell graft on Day 0. Target CD34+ dose 6 x10e6/kg, (range 3 to 8x10e6/kg) CD3+ dose fixed to 2 x 10e4/kg.

Also known as: Peripheral Blood Stem Cell Transplant, HSCT, BMT

allogeneic hematopoietic SCT

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• RECIPIENT:
• \. Ages 10-55 years inclusive (but less than 56)
• \. Chronic myelogenous leukemia (CML) in chronic phase
• \. Acute lymphoblastic leukemia (ALL) categories
• Adults in first remission with high-risk features
• All second or subsequent remissions, primary induction failure, partially responding or untreated relapse
• \. Acute myelogenous leukemia (AML)
• AML in first remission Except AML with good risk karyotypes
• All AML in second or subsequent remission, primary induction failure and resistant relapse
• \. Myelodysplastic syndromes categories
• refractory anemia with transfusion dependence
• refractory anemia with excess of blasts
• transformation to acute leukemia, chronic myelomonocytic leukemia
• \. Myeloproliferative disorders in transformation to acute leukemia
• \. Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 /micro L) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy

You may not qualify if:

• RECIPIENT
• \. Patient pregnant
• \. Age less than 10 years and 56 years or more
• \. Patients with CML in chronic phase who are 41 years or over in whom imatinib mesylate (STI-571)is the treatment of choice
• \. ECOG performance status of 2 or more
• \. Severe psychiatric illness
• \. Major anticipated illness or organ failure incompatible with survival from BMT
• \. DLCO less than 60% predicted
• \. Left ventricular ejection fraction: less than 40%
• \. Serum creatinine greater than 3mg/dl
• \. Serum bilirubin greater than 4 mg/dl
• \. HIV positive 12. Debilitation or age making the risk of intensive myeloablative therapy unacceptable
• DONOR
• \. Pregnant or lactating
• \. Donor unfit to receive G-CSF and undergo apheresis

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Montero A, Savani BN, Shenoy A, Read EJ, Carter CS, Leitman SF, Mielke S, Rezvani K, Childs R, Barrett AJ. T-cell depleted peripheral blood stem cell allotransplantation with T-cell add-back for patients with hematological malignancies: effect of chronic GVHD on outcome. Biol Blood Marrow Transplant. 2006 Dec;12(12):1318-25. doi: 10.1016/j.bbmt.2006.08.034.

  PMID: 17162214 RESULT

• Montero A, Savani BN, Kurlander R, Read EJ, Leitman SF, Childs R, Solomon SR, Barrett AJ. Lineage-specific engraftment and outcomes after T-cell-depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning. Br J Haematol. 2005 Sep;130(5):733-9. doi: 10.1111/j.1365-2141.2005.05665.x.

  PMID: 16115130 RESULT

• McIver ZA, Yin F, Hughes T, Battiwalla M, Ito S, Koklanaris E, Haggerty J, Hensel NF, Barrett AJ. Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival. Bone Marrow Transplant. 2013 Sep;48(9):1192-7. doi: 10.1038/bmt.2013.39. Epub 2013 Mar 25.

  PMID: 23524640 DERIVED

• McIver Z, Melenhorst JJ, Wu C, Grim A, Ito S, Cho I, Hensel N, Battiwalla M, Barrett AJ. Donor lymphocyte count and thymic activity predict lymphocyte recovery and outcomes after matched-sibling hematopoietic stem cell transplant. Haematologica. 2013 Mar;98(3):346-52. doi: 10.3324/haematol.2012.072991. Epub 2012 Oct 12.

  PMID: 23065508 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes; Neoplasms, Plasma Cell; Graft vs Host Disease; Leukemia; Lymphoma, Non-Hodgkin

Interventions

Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Neoplasms by Histologic Type; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Lymphoma

Intervention Hierarchy (Ancestors)

Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Minocher Battiwalla
• Organization: NIH National Heart, Lung and Blood Institute

battiwalla@nhlbi.nih.gov

301-402-4170

Study Officials

• Minocher Battiwalla, MD

  NIH National Heart, Lung, and Blood Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Clinician

Study Record Dates

• First Submitted: March 8, 2004
• First Posted: March 10, 2004
• Study Start: January 1, 2004
• Primary Completion: December 1, 2008
• Study Completion: September 1, 2011
• Last Updated: October 26, 2015
• Results First Posted: May 28, 2012

Record last verified: 2014-06

Locations

US (1)